AU2004298781B2 - Stabilized interferon liquid formulations - Google Patents
Stabilized interferon liquid formulations Download PDFInfo
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- AU2004298781B2 AU2004298781B2 AU2004298781A AU2004298781A AU2004298781B2 AU 2004298781 B2 AU2004298781 B2 AU 2004298781B2 AU 2004298781 A AU2004298781 A AU 2004298781A AU 2004298781 A AU2004298781 A AU 2004298781A AU 2004298781 B2 AU2004298781 B2 AU 2004298781B2
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- beta
- ifn
- composition according
- interferon
- concentration
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- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/40—Cyclodextrins; Derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
Landscapes
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- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
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- Oncology (AREA)
- Communicable Diseases (AREA)
- Virology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
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PCT/EP2004/053407 WO2005058346A1 (en) | 2003-12-11 | 2004-12-10 | Stabilized interferon liquid formulations |
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RS (1) | RS52218B (de) |
SI (1) | SI1691825T1 (de) |
WO (1) | WO2005058346A1 (de) |
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TWI272948B (en) * | 2003-05-01 | 2007-02-11 | Ares Trading Sa | HSA-free stabilized interferon liquid formulations |
JP2007538048A (ja) * | 2004-05-17 | 2007-12-27 | アレス トレーディング ソシエテ アノニム | ヒドロゲル・インターフェロン製剤 |
CN103965347B (zh) | 2007-05-02 | 2017-07-18 | Ambrx公司 | 经修饰干扰素β多肽和其用途 |
EP2170268A2 (de) | 2007-06-25 | 2010-04-07 | Amgen, Inc. | Zusammensetzungen von spezifischen bindungsmitteln für den hepatozyten-wachstumsfaktor |
CA2707840A1 (en) | 2007-08-20 | 2009-02-26 | Allozyne, Inc. | Amino acid substituted molecules |
BRPI0821029A2 (pt) * | 2007-12-20 | 2015-06-16 | Merck Serono Sa | Fomulações de peg-interferon-beta |
US20100203014A1 (en) * | 2009-02-04 | 2010-08-12 | Aegis Therapeutics Llc | Zwitterionic buffered acidic peptide and protein formulations |
EA201590790A1 (ru) | 2012-10-26 | 2015-08-31 | Люпин Лимитед | СТАБИЛЬНАЯ ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ОСНОВЕ PEG-ИНТЕРФЕРОНА АЛЬФА-2b |
GB201604124D0 (en) * | 2016-03-10 | 2016-04-27 | Ucb Biopharma Sprl | Pharmaceutical formulation |
BR112020005703A2 (pt) | 2017-09-27 | 2020-10-20 | Novartis Ag | formulação parentérica compreendendo siponimod |
CN111494611A (zh) * | 2020-06-08 | 2020-08-07 | 长春生物制品研究所有限责任公司 | 一种卡式瓶多剂量笔式注射组合包装的干扰素注射液 |
CN113797317B (zh) * | 2021-10-26 | 2024-01-09 | 科兴生物制药股份有限公司 | 一种组合物及其制备方法和应用 |
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US5997856A (en) * | 1988-10-05 | 1999-12-07 | Chiron Corporation | Method and compositions for solubilization and stabilization of polypeptides, especially proteins |
WO2003002152A2 (en) * | 2001-06-29 | 2003-01-09 | Maxygen Aps | Stabilized formulations of interferons with sulfoalkyl ether cyclodextrins |
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US6582728B1 (en) | 1992-07-08 | 2003-06-24 | Inhale Therapeutic Systems, Inc. | Spray drying of macromolecules to produce inhaleable dry powders |
US5814485A (en) * | 1995-06-06 | 1998-09-29 | Chiron Corporation | Production of interferon-β (IFN-β) in E. coli |
ZA9610374B (en) * | 1995-12-11 | 1997-06-23 | Elan Med Tech | Cartridge-based drug delivery device |
JP2001526033A (ja) * | 1997-12-08 | 2001-12-18 | ジェネンテク・インコーポレイテッド | ヒトインターフェロン−イプシロンというi型インターフェロン |
US6887462B2 (en) * | 2001-04-09 | 2005-05-03 | Chiron Corporation | HSA-free formulations of interferon-beta |
TWI272948B (en) | 2003-05-01 | 2007-02-11 | Ares Trading Sa | HSA-free stabilized interferon liquid formulations |
JP2007538048A (ja) | 2004-05-17 | 2007-12-27 | アレス トレーディング ソシエテ アノニム | ヒドロゲル・インターフェロン製剤 |
JP4988562B2 (ja) | 2004-06-01 | 2012-08-01 | アレス トレーディング ソシエテ アノニム | 安定化したインターフェロン液体製剤 |
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2004
- 2004-12-10 CA CA002547822A patent/CA2547822A1/en not_active Withdrawn
- 2004-12-10 RS RS20110581A patent/RS52218B/en unknown
- 2004-12-10 AT AT04820468T patent/ATE526032T1/de active
- 2004-12-10 WO PCT/EP2004/053407 patent/WO2005058346A1/en active Application Filing
- 2004-12-10 BR BRPI0416980-8A patent/BRPI0416980A/pt not_active IP Right Cessation
- 2004-12-10 PT PT04820468T patent/PT1691825E/pt unknown
- 2004-12-10 JP JP2006543556A patent/JP4658961B2/ja active Active
- 2004-12-10 ES ES04820468T patent/ES2374530T3/es active Active
- 2004-12-10 SI SI200431761T patent/SI1691825T1/sl unknown
- 2004-12-10 DK DK04820468.9T patent/DK1691825T3/da active
- 2004-12-10 PL PL04820468T patent/PL1691825T3/pl unknown
- 2004-12-10 US US10/582,027 patent/US7846427B2/en active Active
- 2004-12-10 EP EP04820468A patent/EP1691825B1/de active Active
- 2004-12-10 AU AU2004298781A patent/AU2004298781B2/en active Active
-
2006
- 2006-05-30 IL IL176021A patent/IL176021A0/en active IP Right Grant
- 2006-07-04 NO NO20063108A patent/NO20063108L/no not_active Application Discontinuation
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2011
- 2011-09-30 HR HR20110699T patent/HRP20110699T1/hr unknown
- 2011-12-06 CY CY20111101217T patent/CY1112193T1/el unknown
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5997856A (en) * | 1988-10-05 | 1999-12-07 | Chiron Corporation | Method and compositions for solubilization and stabilization of polypeptides, especially proteins |
WO2003002152A2 (en) * | 2001-06-29 | 2003-01-09 | Maxygen Aps | Stabilized formulations of interferons with sulfoalkyl ether cyclodextrins |
Also Published As
Publication number | Publication date |
---|---|
NO20063108L (no) | 2006-07-04 |
EP1691825A1 (de) | 2006-08-23 |
ATE526032T1 (de) | 2011-10-15 |
US7846427B2 (en) | 2010-12-07 |
PL1691825T3 (pl) | 2012-02-29 |
CA2547822A1 (en) | 2005-06-30 |
SI1691825T1 (sl) | 2011-12-30 |
JP2007513925A (ja) | 2007-05-31 |
DK1691825T3 (da) | 2011-12-05 |
ES2374530T3 (es) | 2012-02-17 |
WO2005058346A1 (en) | 2005-06-30 |
CY1112193T1 (el) | 2015-12-09 |
JP4658961B2 (ja) | 2011-03-23 |
PT1691825E (pt) | 2011-10-12 |
RS52218B (en) | 2012-10-31 |
AU2004298781A1 (en) | 2005-06-30 |
IL176021A0 (en) | 2006-10-05 |
HRP20110699T1 (hr) | 2011-10-31 |
BRPI0416980A (pt) | 2007-02-21 |
EP1691825B1 (de) | 2011-09-28 |
US20070104682A1 (en) | 2007-05-10 |
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